Between normal appearing ductal structures are linearly arranged streams of round cells.

The hallmark of infiltrative lobular carcinoma is the single-filing of tumor cells. Desmoplastic response may be minimal or absent.

A higher power of single-filing cells. The nuclei are generally small, round or oval, sometimes with eccentrically placed nuclei, giving a signet ring look. In this image, there is little pleomorphism and no mitotic figures, favoring the diagnosis of the classic type of lobular carinoma.

For comparison, this example which shows infiltrating ductal carcinoma with areas of lobular growth pattern. Note that the these files are more than one cell in width, streaming through a desmoplastic stroma.

The cell block clearly demonstrates the discohesiveness of the lesional cells.

ER stain on cell block demonstrates ER positivity. Note that most lobular carcinomas are ER and PR positive with no Her2/neu overexpression. These features are flipped in pleomorphic, high-grade lesions.

Low power very cellular Image

some patternless, some lining up Image

a few cells with cytoplasmic mucin vacuole Image

Invasive lobular carcinomas constitute ~10-15% of invasive breast cancers and is the second most common form of invasive breast cancer. Bilaterality and multicentricity are purported features of lobular carcinomas, however, these issues are still being disputed. The higher likelihood of contralateral mastectomy in women with lobular carcinomas may have created a biased picture. The incidence of lobular carcinomas appear to be rising, possibly due to hormonal replacement therapy in post-menopausal women.1,2

There are several histologic variants of lobular carcinomas which have important prognostic implications.

• Classic (~40%): single-filing or targetoid pattern (forming concentric rings around a duct)of lesions cell
• Alveolar (4-5%): forming rounded nested aggregates
• Tubulo-lobular (5%): overall architecture is that of a single-filing infiltrative or targetoid pattern, except the tumor cells form little tubules. There is some debate whether or not this variant should be listed in the lobular carcinoma family as one study demonstrated e-cadherin expression. These variants tend to have a more favorable outcome, similar to tubular carcinoma (see our case for tubular carcinoma). The tubules in this variant are smaller than those in tubular carcinomas.
• Solid (5%): Infiltrate in dffuse sheets with very little intervening stroma
• Pleomorphic (?%):Larger pleomorphic cells with more abundant cytoplasm in a classic lobular infiltrative pattern.
• Mixed (40%): To be called one of these subtypes, 80-90% of the lesion must demonstrate the characteristic pattern. Otherwise, the tumor can be called a mixed subtype.

Well-differentiated and moderately differentiated lobular carcinomas express ER and PR receptors, without overexpression of HER2/neu. However, poorly-differentiated lobular carcinomas lack ER and PR receptors and may overexpress HER2/neu. Lobular carcinomas and LCIS demonstrate loss in a region of chromosome 6 responsible for cell-adhesion, which includes the genes for e-cadherin and B-catenin. Inactivation (by mutation or methylation) of e-cadherin on the opposite allele results in a lack of e-cadherin expression.1,3

Presents similarly to NST as a palpable mass or a density on mammogram, however, a minority of cases may present as a vague, ill-defined thickening of the breast with subtle changes on mammogram due to an infiltrative tumor without a desmoplastic response.2 Also, there is less of an association with microcalcifications than NST.

The histologic subtype is a prognostic factor. The tubulo-lobular variant has the most favorable outcome of the group, with a 17% risk of local recurrence and 13% risk of distant metastasis. In comparison, the solid variant has a 82% risk of local recurrence and 54% risk of distant metatstasis. The 12 year survival of tubulo-lobular variant is 100% versus 47% for the solid subtype.2 The pleomorphic variant carries a worse prognosis, as it is a variant with high-grade features by definition.

Lobular carcinomas have a unique pattern of metastasis, favoring the the GI tract, ovaries, leptomeninges, uterus and CSF. They do not favor the lungs and pleura (like NST).

• Lobular : Lobular Carcinoma in Situ, Pleomorphic Variant